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Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

Ruvolo G, Pisano C, Candore G, Lio D, Palmeri C, Maresi E, Balistreri CR - Mediators Inflamm. (2014)

Bottom Line: In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA.Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing.It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

View Article: PubMed Central - PubMed

Affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.

ABSTRACT
Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

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Related in: MedlinePlus

Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in tissue samples of the control aortas and patients and normal aorta case areas. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases showed significant higher numbers of these cells than controls and normal aorta case areas.
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fig2: Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in tissue samples of the control aortas and patients and normal aorta case areas. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases showed significant higher numbers of these cells than controls and normal aorta case areas.

Mentions: Histopathological investigations were performed only in 100 aorta samples obtained from aortic wall of patients who underwent surgical repair, since some patient's aortas showed unsuitable histological conditions. The procedures used were previously reported in our recent studies [16, 46–49] and briefly described in online Supplementary Material. In addition, the following histological features were evaluated: (1) fibrosis (defined as an increase in interstitial collagen); (2) medionecrosis (defined as a focal loss of smooth muscle cell nuclei in the media); (3) cystic medial necrosis (defined as mucoid material accumulation); (4) focal or plurifocal medial apoptosis; (5) elastic fragmentation (defined as focal fragmentation of elastic lamellae in the media); (6) amounts of MMP-9; (7) inflammatory/immune cell infiltration. Histopathological abnormalities of aortic wall were graded and defined according to the definitions and grading systems used by Bechtel and colleagues [50] (see details reported in the section of online Supplementary Materials and precisely in Figures 1(S) and 2(S).) and previously described in our recent studies [16, 46–49].


Can the TLR-4-mediated signaling pathway be "a key inflammatory promoter for sporadic TAA"?

Ruvolo G, Pisano C, Candore G, Lio D, Palmeri C, Maresi E, Balistreri CR - Mediators Inflamm. (2014)

Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in tissue samples of the control aortas and patients and normal aorta case areas. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases showed significant higher numbers of these cells than controls and normal aorta case areas.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4120489&req=5

fig2: Morphometric quantification of lymphocytes, T cell subpopulations, and macrophages in tissue samples of the control aortas and patients and normal aorta case areas. CD3, CD4, CD8, CD20, and CD68 positive cells in media and adventitia and in 10 contiguous high-power fields (magnification 400x) were counted by two independent observers. Significant increased amounts of CD3+CD4+CD8+CD68+CD20+ cells were observed by comparing their values among the three groups (by ANOVA test). In particular, cases showed significant higher numbers of these cells than controls and normal aorta case areas.
Mentions: Histopathological investigations were performed only in 100 aorta samples obtained from aortic wall of patients who underwent surgical repair, since some patient's aortas showed unsuitable histological conditions. The procedures used were previously reported in our recent studies [16, 46–49] and briefly described in online Supplementary Material. In addition, the following histological features were evaluated: (1) fibrosis (defined as an increase in interstitial collagen); (2) medionecrosis (defined as a focal loss of smooth muscle cell nuclei in the media); (3) cystic medial necrosis (defined as mucoid material accumulation); (4) focal or plurifocal medial apoptosis; (5) elastic fragmentation (defined as focal fragmentation of elastic lamellae in the media); (6) amounts of MMP-9; (7) inflammatory/immune cell infiltration. Histopathological abnormalities of aortic wall were graded and defined according to the definitions and grading systems used by Bechtel and colleagues [50] (see details reported in the section of online Supplementary Materials and precisely in Figures 1(S) and 2(S).) and previously described in our recent studies [16, 46–49].

Bottom Line: In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA.Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing.It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

View Article: PubMed Central - PubMed

Affiliation: Unit of Cardiac Surgery, Department of Surgery and Oncology, University of Palermo, 90127 Palermo, Italy.

ABSTRACT
Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR = 14.4, P = 0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments.

Show MeSH
Related in: MedlinePlus